The Influence of Viral Infections on Iron Homeostasis and the Potential for Lactoferrin as a Therapeutic in the Age of the SARS-CoV-2 Pandemic
Abstract
:1. Introduction
2. Iron Homeostasis and Viral Infection
3. Lactoferrin as a Therapeutic Adjuvant in Respiratory Viral Infections
3.1. Bovine Lactoferrin: A Multifunctional Glycoprotein
3.2. Antiviral Activity of Lactoferrin
3.3. Lf as a Therapeutic Adjuvant in COVID-19
3.4. Antiviral Activity of Lactoferrin against SARS-CoV-2
3.5. Clinical Evidence of Lactoferrin Efficacy in COVID-19 Patients
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Author (Year) [Citation] | Model | Lactoferrin Source Route (Dose) | Brief Results |
---|---|---|---|
Sinopoli et al. (2022) [6] | Systemic Review | NA | Systemic review of clinical trials using orally administered Lf for the treatment of viral infections. |
Marchetti et al. (1996) [42] | Primate In vitro | hLf bLf | Lf inhibits HSV1 absorption with bLf showing better efficacy than hLf. |
Lu et al. (1987) [39] | Murine In vivo | hLf i.p. | hLf shown to have protective effects against the polycythemia-inducing strain of the friend virus complex in mice. |
Marchetti et al. (1998) [43] | Primate In vitro | bLf | The antiviral activity of Lf appears to correlate with the degree of its metal binding and saturation. |
Yi et al. (1997) [44] | In vitro | bLf hLf | Demonstrates interaction of Lf and HCV envelope proteins. |
Marchetti et al. (1999) [45] | Primate In vitro | bLf | Suggests bLf plays a role in altering viral infection, particularly in the gut, through the inhibition of certain steps of viral infection. |
Superti et al. (2001) [46] | Primate In vitro | bLf | bLf inhibits rotavirus through a different mechanism than the previously reported for HPV. |
El-Fakharany (2013) [47] | Human In vitro | hLf bLf camel Lf sheep Lf | Human, camel, bovine, and sheep Lf prevent HCV entry into cells by binding the virus; camel Lf was most effective. |
Hara et al. (2002) [48] | Human In vitro | bLf hLf | Lf inhibits HBV infection in vitro. |
Ishii et al. (2003) [49] | Human Clinical | bLf oral (0.6 g/day) | Increased IL-18 with oral bLf supplement in chronic HCV patients. |
Okada et al. (2002) [40] | Human Clinical | bLf oral (1.8–7.2 g/day) | bLf use in chronic hepatitis C patients is well tolerated. |
El-Ansary et al. (2016) [50] | Human Clinical | bLf oral (0.5 g/day) | Increased CD4, CD8, CD137, and CD56 levels with bLf supplementation in chronic HCV patients |
Ueno et al. (2006) [41] | Humans Clinical | bLf oral (1.8 g/day) | Oral Lf has a negligible impact on viral load when taken orally by patients with chronic HCV. |
Tanaka et al. (1999) [51] | Humans Clinical | bLf oral (1.8–6 g/day) | Lf could be used as an anti-HCV adjuvant therapy with the potential to help treat chronic hepatitis. |
Hirashima et al. (2004) [52] | Human Clinical | bLf oral (9.0 g/day) | Lf did not increase the response rate or prevent relapse after discontinuing interferon in chronic HCV patients. |
Ishibashi et al. (2005) [53] | Human Clinical | bLf oral (0.6 g/day) | This study failed to demonstrate that Lf in combination with antiviral therapy provided additional benefit to chronic HCV patients. |
Kaito et al. (2007) [54] | Human Clinical | bLF oral (3.6 g/day) | Lf was shown to increase the effectiveness of interferon and ribavirin therapy in chronic HCV patients. |
Konishi et al. (2006) [55] | Human Clinical | bLf oral (3.6 g/day) | Decreased ALT levels and plasma 8-isoprostane in chronic HCV patients. |
Ochoa et al. (2013) [56] | Human Clinical | bLf oral (0.5 g/day) | Decreased duration and symptoms in norovirus patients. |
Egashira et al. (2007) [57] | Human Clinical | bLf oral (100 mg/day) | Decreased frequency and duration of symptoms in rotavirus patients. |
Zuccotti et al. (2007) [58] | Human Clinical | bLf oral (3 g/day) | Observed decline in viral load during bLf administration in HIV patients. |
Mirabelli et al. (2020) [59] | Human Primate In vitro | bLf hLf | Lf effective, in vitro, at inhibiting COVID through multiple mechanisms. |
Salaris et al. (2021) [60] | Human Primate In vitro | bLf | Lf-moderated immunity during SARS-CoV-2 infection. |
Oda et al. (2021) [61] | Human In vitro | bLF | bLf demonstrates antiviral activity against the human norovirus |
Wotring et al. (2022) [62] | Human In vitro | bLf | Dairy product efficacy in inhibiting SARS-CoV-2 infection was dependent on Lf concentration; bLf retained efficacy against SARS-CoV-2 viral variants of concern. |
Miotto et al. (2021) [63] | In silico | hLF | Computational modeling indicated that Lf blocks SARS-CoV-2 infection through competitive binding with the spike protein. |
Piacentini et al. (2022) [64] | In silico | hLf | Lf binds to ACE2 receptor and not SARS-CoV-2 spike protein RBD. |
Campione et al. (2021) [65] | Human Primate In vitro | bLf | Lf effective antiviral against SARS-CoV-2 infection in vitro. |
Cutone et al. (2022) [66] | Human In vitro | bLf | Preincubation with bLf inhibited SARS-CoV-2 binding and pseudovirus entry into epithelial and macrophage-like cells, reduced inflammatory response, and increased gene expression associated with iron homeostasis. |
Serrano et al. (2020) [67] | Human Clinical | bLf oral (20–30 mg/day) | Improvement in reported symptoms in mild to moderate COVID-19 patients. |
Campione et al. (2020) [68] | Human Clinical | bLf oral (1 g/day) | Decreased time to negative molecular test and duration of symptoms in COVID-19 patients |
Algahtani et al. (2021) [69] | Human Clinical | bLf oral (200–400 mg/day) | No statistical difference between treatment and non-treatment groups, but trends in symptom improvement and blood biomarker profile observed. |
Rosa et al. (2021) [70] | Human Clinical | bLf oral (200–1000 mg/day) | Reduced time to negative molecular SARS-CoV-2 test, reported reduction in symptoms of COVID-19 patients of advanced age. |
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Ward, J.L.; Torres-Gonzalez, M.; Ammons, M.C.B. The Influence of Viral Infections on Iron Homeostasis and the Potential for Lactoferrin as a Therapeutic in the Age of the SARS-CoV-2 Pandemic. Nutrients 2022, 14, 3090. https://doi.org/10.3390/nu14153090
Ward JL, Torres-Gonzalez M, Ammons MCB. The Influence of Viral Infections on Iron Homeostasis and the Potential for Lactoferrin as a Therapeutic in the Age of the SARS-CoV-2 Pandemic. Nutrients. 2022; 14(15):3090. https://doi.org/10.3390/nu14153090
Chicago/Turabian StyleWard, Jeffrey L., Moises Torres-Gonzalez, and Mary Cloud B. Ammons. 2022. "The Influence of Viral Infections on Iron Homeostasis and the Potential for Lactoferrin as a Therapeutic in the Age of the SARS-CoV-2 Pandemic" Nutrients 14, no. 15: 3090. https://doi.org/10.3390/nu14153090